Atory and neurologic disease in horses and humans in Hendra, a suburb of Brisbane, Australia[2]. To date, there have now been 39 recorded outbreaks of HeV infections, 25 of these in just the past two years the most recent in September of 2012 [3], all causing lethal respiratory disease 1379592 and encephalitis in horses. Five of these events have also involved a total of seven human cases four of which were fatal [4?]. Infections of NiV have also repeatedly occurred involving hundreds of human cases since its emergence in 1998 in a large outbreak of disease in humans and pigs, and there have been at least thirteen recognized occurrences in Bangladesh and India since 2001 the most recent in January of 2012[2]. The natural reservoir hosts of both HeV and NiV are fruit bats, predominantly several species of Pteropid bats (family Pteropodidae) [4]. The henipaviruses also possess a unique and very broad species tropism documented by both natural and experimental infections and in addition to bats, humans, horses and pigs, they can infect and cause disease in guinea pigs, hamsters, cats, dogs (reviewed in [4]), ferrets [8] and nonhuman primates [9,10]. Because of their highly pathogenic characteristics and lackof any approved therapeutic approaches, the henipaviruses are classified as select agents and biosafety level 4 (BSL-4) pathogens [11]. For many enveloped viruses, entry is mediated by viral fusion glycoproteins that contain two distinct activities: receptor attachment and membrane fusion. The fusion activity is triggered either by receptor binding or exposure to an acidic environment following endocytosis [12]. In the Salmon calcitonin chemical information paramyxovirus family, the attachment and membrane fusion activities are performed by two separate envelope glycoproteins [13]. The henipaviruses possess an attachment (G) and a fusion (F) glycoprotein which together work in concert to mediate the virus attachment and entry process, but the precise triggering mechanism of paramyxovirus fusion has yet to be defined in detail [14,15]. The henipavirus G glycoproteins have a type-II transmembrane topology, containing a short N-terminal cytoplasmic tail and a long C-terminal extracellular globular head. These two domains are connected by transmembrane and extracellular stem regions, and membrane anchored G forms disulfide-linked dimers which associate in pairs as a tetrameric oligomer [16]. Distinct from most other members within the subfamily Paramyxovirinae, the henipavirus attachment glycoprotein does not hemagglutinate and neither binds to sialic acid, nor retains neuraminidase activity, and instead binds cell surface protein receptors [1]. Recently, ephrin-B2 and ephrin-B3 were identified as the functional receptors for both HeV and NiVHendra Virus Entry Mechanism Implied by Structure[17?0]. The F glycoprotein is 1527786 a type-I transmembrane protein, which is initially synthesized as a precursor F0 which form trimeric oligomers that are then proteolytically processed into the disulphide-linked subunits F1 and F2 [21]. The direct association between paramyxovirus attachment glycoproteins with their respective F glycoprotein has also been reported, and important elements for this feature have been mapped to several sites in both the stem regions and the globular head domains among several virus species [22?1]. The pre-fusion trimeric F glycoprotein is proposed to be in a “metastable” conformation and associated with its oligomeric attachment glycoprotein Gracillin chemical information partner. A current, and widely a.Atory and neurologic disease in horses and humans in Hendra, a suburb of Brisbane, Australia[2]. To date, there have now been 39 recorded outbreaks of HeV infections, 25 of these in just the past two years the most recent in September of 2012 [3], all causing lethal respiratory disease 1379592 and encephalitis in horses. Five of these events have also involved a total of seven human cases four of which were fatal [4?]. Infections of NiV have also repeatedly occurred involving hundreds of human cases since its emergence in 1998 in a large outbreak of disease in humans and pigs, and there have been at least thirteen recognized occurrences in Bangladesh and India since 2001 the most recent in January of 2012[2]. The natural reservoir hosts of both HeV and NiV are fruit bats, predominantly several species of Pteropid bats (family Pteropodidae) [4]. The henipaviruses also possess a unique and very broad species tropism documented by both natural and experimental infections and in addition to bats, humans, horses and pigs, they can infect and cause disease in guinea pigs, hamsters, cats, dogs (reviewed in [4]), ferrets [8] and nonhuman primates [9,10]. Because of their highly pathogenic characteristics and lackof any approved therapeutic approaches, the henipaviruses are classified as select agents and biosafety level 4 (BSL-4) pathogens [11]. For many enveloped viruses, entry is mediated by viral fusion glycoproteins that contain two distinct activities: receptor attachment and membrane fusion. The fusion activity is triggered either by receptor binding or exposure to an acidic environment following endocytosis [12]. In the paramyxovirus family, the attachment and membrane fusion activities are performed by two separate envelope glycoproteins [13]. The henipaviruses possess an attachment (G) and a fusion (F) glycoprotein which together work in concert to mediate the virus attachment and entry process, but the precise triggering mechanism of paramyxovirus fusion has yet to be defined in detail [14,15]. The henipavirus G glycoproteins have a type-II transmembrane topology, containing a short N-terminal cytoplasmic tail and a long C-terminal extracellular globular head. These two domains are connected by transmembrane and extracellular stem regions, and membrane anchored G forms disulfide-linked dimers which associate in pairs as a tetrameric oligomer [16]. Distinct from most other members within the subfamily Paramyxovirinae, the henipavirus attachment glycoprotein does not hemagglutinate and neither binds to sialic acid, nor retains neuraminidase activity, and instead binds cell surface protein receptors [1]. Recently, ephrin-B2 and ephrin-B3 were identified as the functional receptors for both HeV and NiVHendra Virus Entry Mechanism Implied by Structure[17?0]. The F glycoprotein is 1527786 a type-I transmembrane protein, which is initially synthesized as a precursor F0 which form trimeric oligomers that are then proteolytically processed into the disulphide-linked subunits F1 and F2 [21]. The direct association between paramyxovirus attachment glycoproteins with their respective F glycoprotein has also been reported, and important elements for this feature have been mapped to several sites in both the stem regions and the globular head domains among several virus species [22?1]. The pre-fusion trimeric F glycoprotein is proposed to be in a “metastable” conformation and associated with its oligomeric attachment glycoprotein partner. A current, and widely a.
